The brain maintains constant intracellular levels of T3 by a high-affinity deiodinase called type 2 deiodinase (D2) that is expressed in glial cells of the CNS. D2 has a Km of 1 nM and maintains intracellular concentrations of T3 even when circulating T4 falls to low levels. D2 is also present in pituitary thyrotropes. There, D2 acts as a “thyroid axis sensor” that mediates the ability of circulating T4 to feed back on secretion of thyroid stimulating hormone (TSH). Expression of D2 is increased during hypothyroidism, which helps maintain constant T3 levels in the brain.
There is also an “inactivating” deiodinase called type 3 deiodinase (D3). D3 is a high-affinity inner ring deiodinase that converts T4 to the inactive rT3. Type 3 deiodinase is increased during hyperthyroidism, which helps blunt overproduction of T4. All forms of iodothyronines are eventually further deiodinated to noniodinated thyronine.
Because iodide plays a unique role in thyroid physiology, a description of thyroid hormone synthesis requires some understanding of iodide turnover (
Fig. 42.4 ). An average of 400 µg of iodide per person is ingested daily in the United States, versus a minimum daily requirement of 150 µg for adults, 90 to 120 µg for children, and 200 µg for pregnant women. In the steady state, the same amount, 400 µg, is excreted in urine. Iodide is actively concentrated in the thyroid gland, salivary glands, gastric glands, lacrimal glands, mammary glands, and choroid plexus. About 70 to 80 µg of iodide is taken up daily by the thyroid gland from a circulating pool that contains approximately 250 to 750 µg of iodide. The total iodide content of the thyroid gland averages 7500 µg, virtually all of which is in the form of stored iodothyronine in colloid thyroglobulin. In the steady state, 70 to 80 µg of iodide, or about 1% of the total, is released from the gland daily. Of this amount, 75% is secreted as thyroid hormone and the remainder as free iodide. The large ratio (100:1) of iodide stored in the form of hormone to the amount turned over daily protects against iodide deficiency for about 2 months. Iodide is also conserved by a marked reduction in renal excretion of iodide as its concentration in serum falls.
•Fig. 42.2 Histologyofthethyroidglandatlow(upper panel) andhigh(lower panel) magnification.C,colloid;F,thyroidfollicles;S,connectivetissuesepta.(FromYoungBetal.Wheater’s Functional Histology. 5thed.Philadelphia:ChurchillLivingstone;2006.)
CHAPTER 42 The Thyroid Gland
Overview of Thyroid Hormone Synthesis
To understand thyroid hormone synthesis and secretion, one must appreciate the directionality of each process as it relates to the polarized thyroid epithelial cell (
Fig. 42.5 ). Synthesis of thyroid hormone requires two precursors: iodide and thyroglobulin. Iodide is transported across cells from the basal (vascular) side to the apical (follicular luminal) side of the thyroid epithelium. Thyroglobulin is synthesized and secreted across the apical membrane into the follicular lumen. Thus synthesis involves a basal-to-apical movement of these precursors into the follicular lumen (see
Fig. 42.5 ). Actual synthesis of iodothyronines occurs enzymatically within the follicular lumen close to the apical membrane of the epithelial cells (see